Journal ArticleDOI
Mechanisms and consequences of Jak–STAT signaling in the immune system
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TLDR
Recent advances in Jak–STAT biology are reviewed, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent TFs.Abstract:
Kinases of the Jak ('Janus kinase') family and transcription factors (TFs) of the STAT ('signal transducer and activator of transcription') family constitute a rapid membrane-to-nucleus signaling module that affects every aspect of the mammalian immune system. Research on this paradigmatic pathway has experienced breakneck growth in the quarter century since its discovery and has yielded a stream of basic and clinical insights that have profoundly influenced modern understanding of human health and disease, exemplified by the bench-to-bedside success of Jak inhibitors ('jakinibs') and pathway-targeting drugs. Here we review recent advances in Jak-STAT biology, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent TFs.read more
Citations
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Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality.
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IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy.
TL;DR: This Review focuses on recent advances in the understanding of the transcriptional, chromatin-based and metabolic mechanisms that underlie IFNγ-mediated polarization of macrophages to an ‘M1-like’ state, which is characterized by increased pro-inflammatory activity and macrophage resistance to tolerogenic and anti-inflammatory factors.
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Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer
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Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens
Atray Dixit,Atray Dixit,Oren Parnas,Biyu Li,Jenny Chen,Jenny Chen,Charles P. Fulco,Charles P. Fulco,Livnat Jerby-Arnon,Nemanja D. Marjanovic,Nemanja D. Marjanovic,Danielle Dionne,Tyler Burks,Raktima Raychowdhury,Britt Adamson,Thomas M. Norman,Eric S. Lander,Eric S. Lander,Eric S. Lander,Jonathan S. Weissman,Jonathan S. Weissman,Nir Friedman,Nir Friedman,Aviv Regev,Aviv Regev,Aviv Regev +25 more
TL;DR: Perturb-seq accurately identifies individual gene targets, gene signatures, and cell states affected by individual perturbations and their genetic interactions, and posit new functions for regulators of differentiation, the anti-viral response, and mitochondrial function during immune activation.
References
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Journal ArticleDOI
Activating STAT6 mutations in follicular lymphoma.
Mehmet Yildiz,Hongxiu Li,Denzil Bernard,Nisar A. Amin,Peter Ouillette,Si�n Jones,Kamlai Saiya-Cork,Brian Parkin,Kathryn Jacobi,Kerby Shedden,Shaomeng Wang,Alfred E. Chang,Mark S. Kaminski,Sami N. Malek +13 more
TL;DR: The genetic and functional data combined strengthen the recognition of the IL-4/JAK/STAT6 axis as a driver of FL pathogenesis.
Journal ArticleDOI
New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases
TL;DR: The possible links among RTK trafficking, signaling, and degradation in leukemic cells are discussed and different mechanisms prevent the termination of the signal, which normally occurs through receptor ubiquitination and degradation.
Journal ArticleDOI
CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance
Eva Maria Putz,Dagmar Gotthardt,Gregor Hoermann,Agnes Csiszar,Silvia Wirth,Angelika Berger,Elisabeth Straka,Doris Rigler,Barbara Wallner,Amanda M. Jamieson,Winfried F. Pickl,Eva Zebedin-Brandl,Mathias Müller,Thomas Decker,Veronika Sexl +14 more
TL;DR: It is shown that mutation of a single phosphorylation site (Stat1-S727A) enhances NK cell cytotoxicity against a range of tumor cells, accompanied by increased expression of perforin and granzyme B.
Journal ArticleDOI
Immunocytokines for cancer treatment: past, present and future
Dario Neri,Paul M. Sondel +1 more
TL;DR: This review presents relevant concepts and strategies for the design and use of anticancer immunocytokine products and discusses emerging Strategies for the pharmaceutical development and clinical application of this promising class of biopharmaceuticals.
Journal ArticleDOI
The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates TH17 differentiation
Dan Lu,Liang Liu,Xin Ji,Yanan Gao,Xi Chen,Yu Liu,Liu Yang,Xuyang Zhao,Yan Li,Yunqiao Li,Yan Jin,Yu Zhang,Michael A. McNutt,Yuxin Yin +13 more
TL;DR: It is found that the phosphatase DUSP2 (PAC1) negatively regulated the development of TH17 cells and was directly associated with the signal transducer and transcription activator STAT3 and attenuated its activity through dephosphorylation of STAT3 at Tyr705 and Ser727.